Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers

Purpose An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers from numerous thyroid cancer expression profiling studies. Materials and Methods To address this challenge, we have carried out a comprehensive meta-review of thyroid cancer biomarkers from 21 published studies. A gene ranking system that considers the number of comparisons in agreement, total number of samples, average fold-change and direction of change was devised. Results We have observed that genes are consistently reported by multiple studies at a highly significant rate ( P <.05). Comparison with a meta-analysis of studies reprocessed from raw data showed strong concordance with our method. Conclusion Our approach represents a useful method for identifying consistent gene expression markers when raw data are unavailable. A review of the top 12 candidates revealed well known thyroid cancer markers such as MET, TFF3, SERPINA1, TIMP1, FN1, and TPO as well as relatively novel or uncharacterized genes such as TGFA, QPCT, CRABP1, FCGBP, EPS8 and PROS1. These candidates should help to develop a panel of markers with sufficient sensitivity and specificity for the diagnosis of thyroid tumors in a clinical setting.